PROJECT SUMMARY The regulation and mis-regulation of sphingolipid metabolism in acute myeloid leukemia (AML) occurs at multiple bio-molecular levels?gene mutation, enzyme abundances and activities, as well as sphingolipid precursors and products. The innovative aspect of the Program Project has systematically collected deep biomolecular profiles of accrued patient samples and relevant AML cell lines. The new Systems Metabolomics Core (Core C) will help the larger P01 project team to generate testable hypotheses by integrating the systems-level datasets from individual research projects and the other research cores. The goal is to inform critical Project-level decisions involving sphingolipid-targeted therapies. Core C will pursue the following Specific Aims: 1) evaluate linear and nonlinear predictive models of outcome and response based on patient- specific biomolecules and (cyto)genetics; 2) test data-driven predictive models of outcomes and response based on patient-specific, gene?transcript?lipid?activity signatures; and 3) integrate gene, transcript, and metabolite profiles of AML patients with a reconstructed sphingolipid module of the human metabolic network. Core C leadership is comprised of experts in data-driven cancer modeling, metabolic network reconstruction, and systems biology. Therefore, the Core is poised to adapt its approaches to the changing needs of the individual research projects over the second term of the P01.